ABSTRAKLesbian, Gay, Biseksual dan Transgender (LGBT) di Indonesia adalah ke-5 terbesar di dunia setelah China, India, Eropa, dan Amerika. Menurut Kemenkes, sejak tahun 2005 sampai September 2015 terdapat kasus HIV sebanyak 184.929. Salah satu upaya untuk menurunkan angka penyakit menular seksual adalah dengan meningkatkan pengetahuan remaja sehingga merubah pola pikir dan tindakan. Peningkatan pengetahuan dapat dilakukan dengan menggunakan media Cognitive Theory of Multimedia Learning (CTML) yang merupakan perpaduan teks, gambar, grafik, sound, animasi, video dan lain-lain. Tujuan Penelitian mengetahui efektivitas Cognitive Theory of Multimedia Learning dalam peningkatan pengetahuan remaja SMA tentang dampak kesehatan LGBT di Kabupaten Bantul. Jenis penelitian ini quasy eksperiment dengan one group pretest and posttest design. Sampel dalam penelitian ini adalah 315 siswa SMA di Kabupaten Bantul yang dirandomisasi dengan teknik pengundian (Loterry Technique). Instrumen penelitian menggunakan kuesioner dan media pembelajaran CTML. Hasil mean pada pretest yaitu 16, dan mean posttest yaitu 23, Uji Analisis data menggunakan Z test. Hasil Uji analisis dengan nilai Z -10,344 dengan p value sebesar 0,000. Oleh karena p < nilai α 0,05 (0,000 < 0,05) maka disimpulkan terdapat perbedaan bermakna antara pengetahuan pretest dengan pengetahuan posttest. Kesimpulan Cognitive Theory of Multimedia Learning Efektif dalam peningkatan pengetahuan remaja SMA tentang dampak kesehatan LGBT. Kata Kunci: Cognitive Theory of Multimedia Learning; pengetahuan; LGBT remaja ABSTRACTLesbian, Gay, Bisexual and Transgender (LGBT) in Indonesia is the 5th largest in the world after China, India, Europe, and America. According to the Ministry of Health, from 2005 to September 2015 there were 184,929 cases of HIV. The efforts to reduce the rate of sexually transmitted diseases is to increase knowledge to change the mindset and actions. Knowledge improvement can be done by using Cognitive Theory of Multimedia Learning which is a combination of text, images, graphics, sound, animation, video and others. This study was aimed to know the effectiveness of Cognitive Theory of Multimedia Learning in improving the knowledge of high school students about the health impacts of LGBT in Bantul District. This type of research was quasy experimental research with one group pretest and posttest design. The samples in this study were 315 high school students in Bantul District who were domesticated with loterry technique. Research instruments used CTML questionnaires and learning media. Test Data analysis used Z test. The mean result on the pretest is 16, and the mean posttest is 23. The results analysis test with a value of Z -10,344 with a p value of 0.000. Since p < a value of α 0.05 (0.000 < 0.05) it is concluded that there is a meaningful difference between pretest knowledge and posttest knowledge. Conclusion Cognitive Theory of Multimedia Learning Effective in improving the knowledge of high school adolescents about the health impacts of LGBT. Keywords: Cognitive Theory of Multimedia Learning; knowledge; LGBT; adolescent